CADET Pilot
Research type
Research Study
Full title
Children's Adaptive Deep Brain Stimulation for Epilepsy Trial (CADET): Pilot
IRAS ID
294472
Contact name
Martin Tisdall
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 11 months, 28 days
Research summary
The Children’s Adaptive Deep brain stimulation for Epilepsy Trial (CADET) Pilot will investigate the safety and feasibility of deep brain stimulation (DBS) for the treatment of children with Lennox-Gastaut syndrome (a rare yet severe form of childhood epilepsy). This will be a two-centre, single-arm, non-randomised clinical trial that will recruit four children (aged 5-15 years) with drug-resistant Lennox-Gastaut syndrome.
Lay summary of study results:Thank you to the children and families who took part!
Who carried out the research?
Clinicians and scientists from Great Ormond Street Hospital for Children (London), King’s College Hospital (London), University College London and University of Oxford designed and ran the study.
Where was the research done?
The children participating in this study were treated at Great Ormond Street Hospital (London).
Why was this research needed?
Some children have epilepsy that does not respond to medicines. Lennox–Gastaut syndrome (LGS) is an epilepsy syndrome with multiple seizure types, including “drop” seizures that can cause falls. When medications are not effective and when surgery to remove a seizure focus is not possible, these children need other treatment options.
What did we test?
Deep brain stimulation (DBS) sends electrical pulses to a deep brain target using implanted wires and a small battery-powered device. We tested an investigational DBS system called Picostim® (not yet approved for routine NHS care). Picostim® is mounted in the skull, avoids long wires to the chest, and can be recharged non-invasively across the skin.
What happened in the study?
Children counted seizures for 30 days before surgery. After the surgery, the DBS device stayed off for 30 days to allow recovery. It was then switched on for six months. We mainly assessed safety (medical problems) and feasibility (study completion and device charging). We also recorded seizure counts (parent diaries and home video-EEG) and parent questionnaires.
Who took part?
Four children joined. One withdrew before surgery because their seizures improved. Three boys aged 7–12 years received the device and completed six months of stimulation.
What did we find about safety?
No child had neurological harm from surgery or stimulation. We recorded six adverse events, including two serious events. One child developed an infection and wound breakdown at their surgery wound and needed a further operation and antibiotics. He recovered fully and kept the device. Another child was admitted with a chest infection that was not related to the study. In one child two brief episodes of sleepiness occurred when stimulation was started or restarted and resolved within 24 hours.
Was the device practical to use?
Families could recharge the device, but two children had short periods when stimulation stopped because the battery ran down after charging errors. Extra training and an automatic “restart” setting was instigated to reduce this risk. One child’s head shape made charging difficult at first, so we designed a custom charging headset that greatly improved charging success.
What were the results?
All three children had fewer seizures. At six months, parent-recorded seizures reduced by 26%, 43% and 47% compared with baseline. Home video-EEG recordings also showed fewer seizures. Two families reported better seizure severity and quality of life, while one reported worse.
What does this mean?
This was a small, open pilot study, so it cannot prove how effective DBS is for LGS. It does show that Picostim® DBS can be implanted and managed in children, with encouraging early safety findings and signals of possible benefit.
What will happen next?
A larger trial is planned to test effectiveness and longer-term outcomes of using the Picostim® DBS device. 22 children will participate in this next study.
Where can I learn more?
ClinicalTrials.gov: NCT05437393. Contact: Dr Rory Piper (UCL/GOSH): Rory.Piper@ucl.ac.uk
Following a 30-day baseline assessment phase, all children will have insertion of a DBS device that will deliver electrical stimulation to both the right and left the thalami of the brain. The device will be left inactive (switched off) for 30-days to allow the ‘lesioning effect’ of DBS insertion to dissipate. Following, all children will have their devices switched on and will receive a pre-defined regime of stimulation for 6-months. Following the end of the trial (6-months following device activation / 8-months following enrolment into the trial), children will have their devices maintained and managed by their clinical team as per their individual clinical requirements.
The primary objective is to determine the feasibility and safety of the intervention and device. The secondary objectives are to study the efficacy of DBS in reducing the number and severity of seizures, reducing the burden of epileptic activity on electroencephalography (EEG), and improving quality of life.
The trial will use a non-CE marked DBS device (Picostim (Bioinduction Ltd)). This DBS device has a battery that is non-invasively recharged by placing a charger over the skin (avoiding the need for frequent surgical replacements). The DBS device is mounted to the cranium (i.e. the battery/generator sits within a trough made in the skull), hopefully reducing device-associated pain, wire snapping with child growth, and reducing the risk of infection.
REC name
London - Queen Square Research Ethics Committee
REC reference
22/LO/0643
Date of REC Opinion
30 Nov 2022
REC opinion
Further Information Favourable Opinion